Safety and Feasibility of Transperineal Targeted Microwave Ablation for Low- to Intermediate-risk Prostate Cancer

Take Home Message Target microwave ablation (TMA) is a novel focal therapy modality for low- to intermediate-risk prostate cancer involving targeted delivery of microwave energy under magnetic resonance imaging/ultrasound fusion guidance. TMA is performed in a day-case setting with good tolerability and no serious adverse events.


Introduction
In recent years, focal therapy (FT) has emerged as an interesting option for localized low-to intermediate-risk prostate cancer (PCa) with the aim of offering a personalized and less invasive treatment in comparison to radical therapies, reducing functional morbidity while maintaining oncologic efficiency [1]. The principle underlying FT is treatment of the ''index lesion'', the substantial lesion that predicts PCa outcomes and from which other cancer clones can arise [2]. For successful FT, accurate detection of PCa foci via multiparametric magnetic resonance imaging (mpMRI) is essential, although systematic biopsies ensure the most accurate sampling possible [3]. Examples of established FT technologies are high-intensity focused ultrasound (HIFU), cryotherapy, and, more recently, focal laser ablation, vascular targeted photodynamic therapy, and irreversible electroporation. Depending on the FT type, the template ranges from focal ablation up to a ''hockey-stick'' ablation. In general, all FT modalities share a favorable toxicity profile, with most complications classified as mild [4]. Acceptable medium-term cancer control has been reported for men with intermediate-risk disease undergoing focal HIFU or cryotherapy [5].
Targeted microwave ablation (TMA) is a novel FT modality involving targeted delivery of microwave energy under mpMRI/ultrasound guidance using a Koelis Trinity (Koelis, Meylan, France) fusion system. Microwave propagation depends mainly on the permittivity of the medium rather than thermal conductivity or tissue impedance, and causes coagulative necrosis in a more predictable and controllable way in comparison to other energy sources [6].

Patients and methods
We performed a single-center, prospective, interventional phase 1-2 trial to evaluate the outcomes of TMA administered to 11 patients with newly diagnosed low-to intermediate-risk PCa. The study was in accordance with the Declaration of Helsinki and was approved by the local ethics committee (reference 0005732). It was registered on ClinicalTrials.gov as NCT04627896. The inclusion criteria were: a single MRI-

Results
Eleven patients were recruited from September 2020 to March 2022. The median patient age was 67 yr (interquar- tile range [IQR] 18). Median PSA was 5.4 ng/ml (IQR 1.8), median prostate volume was 51 cm 3 (IQR 35), and the median lesion Size on MRI was 10 mm (IQR 4). Ten patients were diagnosed with GG 2 Pca and one with GG 1 disease. The median procedure time was 40 min (IQR 30) and the median ablation time was 6 min (IQR 3), with nine patients needing two TMA sessions to adequately treat the cancer area. Periprocedural and postprocedural outcomes are shown in Table 1. No intraoperative complications were reported. All treatments were performed on a day-case basis and no patients were discharged with a urinary catheter. There were no cases of acute urinary retention. Postoperatively, no grade 2 complications were observed ( Table 2). PSA levels did not significantly vary from baseline across the time points (p = 0.46). No significant changes in IPSS (p = 0.39) or IIEF-5 (p = 0.18) scores were reported, as shown in Figure 1. The postoperative VAS score at 24 h was 0 for all patients.
Our study can be regarded as phase 2a (development) according to the IDEAL recommendations on surgical innovations [10]. As a safety precaution, we chose strict inclusion criteria such as a small lesion size up to 12 mm. One prior feasibility study on transrectal TMA showed that post-treatment necrosis on MRI corresponded well to the predicted ablative zones, with a median largest necrosis dimension of 17.5 mm; the authors found total necrosis of the index tumor on MRI in eight out of ten patients [7]. Another safety measure was a distance of 5 mm from the apex and rectum to minimize the risk of complications. his goal was achieved, with no grade 2 complications observed, in line with the two preliminary studies published so far [7,11]. The decision to use one or two energy delivery cycles was based on the shape of the MRI target and the prostate morphology to guarantee adequate treatment while remaining confined to the prostate to avoid potential complications. With transperineal access, we are able to angulate the probe in the sagittal plane in order to reach a satisfactory needle position more easily and avoid interference from the pubic arch for anterior lesions to a certain extent. However, it is foreseeable that it may not be possible to reach anterior areas for very large prostates, as happens for brachytherapy. In our study, the only two patients with anterior lesions had a prostate volume of 53 and 19 cm 3 . The issue of prostate size limits should be evaluated in further studies.
The median operative time was just 40 min, which is shorter than for most FT modalities. We performed almost all procedures under spinal anesthesia, but we showed the feasibility of TMA under sedation. Thanks to the precise organ-based tracking, the urethra was easily spared and there was no need for a urinary catheter postoperatively, minimizing discomfort for patients.

Conclusions
In conclusion, our study shows the safety, feasibility, and good tolerability of TMA for selected patients with PCa. Oncological outcomes are still awaited.
Author contributions: Marco Oderda had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Oderda.
Analysis and interpretation of data: Oderda, Marquis.
Drafting of the manuscript: Oderda.
Critical revision of the manuscript for important intellectual content: Calleris, Faletti, Marra.
Administrative, technical, or material support: None.